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Original Article

Exp Neurobiol 2018; 27(3): 226-237

Published online June 30, 2018

https://doi.org/10.5607/en.2018.27.3.226

© The Korean Society for Brain and Neural Sciences

Morin Prevents Granule Cell Dispersion and Neurotoxicity via Suppression of mTORC1 in a Kainic Acid-induced Seizure Model

Ji Min Lee1†, Jungwan Hong2†, Gyeong Joon Moon1†, Un Ju Jung3, So-Yoon Won4 and Sang Ryong Kim1,2*

1School of Life Sciences, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, 2Brain Science and Engineering Institute, Kyungpook National University, Daegu 41944, 3Department of Food Science and Nutrition, Pukyong National University, Busan 48513, 4Department of Biochemistry and Medical Research Center, Chungbuk National University, Cheongju 28644, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-53-950-7362, FAX: 82-53-943-2762
e-mail: srk75@knu.ac.kr
These authors contributed equally.

Received: March 6, 2018; Revised: May 24, 2018; Accepted: May 25, 2018

An abnormal reorganization of the dentate gyrus and neurotoxic events are important phenotypes in the hippocampus of patients with temporal lobe epilepsy (TLE). The effects of morin, a bioflavonoid constituent of many herbs and fruits, on epileptic seizures have not yet been elucidated, though its beneficial effects, such as its anti-inflammatory and neuroprotective properties, are well-described in various neurodegenerative diseases. In the present study, we investigated whether treatment with morin hydrate (MH) can reduce the susceptibility to seizures, granule cell dispersion (GCD), mammalian target of rapamycin complex 1 (mTORC1) activity, and the increases in the levels of apoptotic molecules and inflammatory cytokines in the kainic acid (KA)-induced seizure mouse model. Our results showed that oral administration of MH could reduce susceptibility to seizures and lead to the inhibition of GCD and mTORC1 activity in the KA-treated hippocampus. Moreover, treatment with MH significantly reduced the increased levels of apoptotic signaling molecules and pro-inflammatory mediators in the KA-treated hippocampus compared with control mice, suggesting a neuroprotective role. Therefore, these results suggest that morin has a therapeutic potential against epilepsy through its abilities to inhibit GCD and neurotoxic events in the in vivo hippocampus.

Graphical Abstract


Keywords: Morin, Seizure, Granule cell dispersion, Kainic acid, Neuroprotection